Efficacy of Several Oximes on Organophosphorus Poisoning Sumie Yamanaka, Yuji Suyama and Masao Nishimura Department of Hygiene, Tokyo Dental College,
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1 Efficacy of Several Oximes on Organophosphorus Poisoning Sumie Yamanaka, Yuji Suyama and Masao Nishimura Department of Hygiene, Tokyo Dental College, Tokyo Various organophosphorus compounds, particularly those with low acute toxicity levels, such as Fenitrothion (common name; Sumithion), Fenthion (common name; Baycid) and Pyridaphenthion (common name; Ofunack), are widely used as insecticides around the world. PAM (2-Pyridinum aldoxime methiodide), the specific antidote against Parathion, is not very effective against poisoning by these organophosphates. This paper reports on the efficacy of PAM and other oximes (Pro-PAM, Toxogonin, TMB-4, and PAD) on toxic symptoms and inhibition of ChE (Cholinesterase) by organophosphates (Dichlorvos, Fenthion, Fenitrothion and Pyridaphenthion). The results were as follows. 1. PAD, a high lipid soluble oxime, was not suitable as an antidote against organophosphorus poisoning because it caused irritation and had its own high toxicity. 2. TMB-4 reactivated blood ChE inhibited by organophosphates to the same level as PAM. But the oxime is no practical use as an antagonist because of high toxicity. 3. Pro-PAM, the prodrug of PAM, and Toxogonin, which has been used practically in Germany, could lighten the toxic symptoms of organophosphorus poisoning to the same level as PAM. The efficacy of these oximes was maintained for 2-3hrs. 4. Pro-PAM, Toxogonin and PAM were able to reactivate blood ChE inhibited by Pyridaphenthion and Fenitrothion, but these oximes couldn't reactivate ChE in brain and other tissues. 5. There was no difference in the antidotal action of PAM, Pro-PAM and Toxogonin because of the same reactivation level of blood ChE and the same recovery pattern of serum ChE isoenzyme. Therefore, it became clear that Pro-PAM and Toxogonin were not more effective against organophosphorus poisoning than PAM. It seemed that a continuous dose of PAM was more effective, and furthermore, that the antidotal effect of PAM should be potentiated by atropine and other therapy. Key words: Organophosphorus poisoning, PAM, Toxogonin, Pro-PAM, Cholinesterase
2 Table 1 Trade names, chemical names and LD50 values of organophosphorus compounds used in this experiment.
3 Table 2 Chemical structure and acute toxicity of oximes used in this experiment.
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8 Fig. 6 Effects of oximes on serum ChE isoenzyme of rats at 3hrs after administration of Pyridaphenthion. Oximes were given 10mins after Pyridaphenthion. Fig. 8 Effects of oximes on serum ChE isoenzyme of rats at 90mins after administration of Fenitrothion. Oximes were given 10mins after Fenitrothion. Fig. 7 Effects of oximes on serum ChE isoenzyme of rats at 21hrs after administration of Pyridaphenthion. Oximes were given 18hrs after Pyridaphenthion.
9 4) Skrinjaric-Spoljar, M., Simeon, V. and Reiner, E.: with HI-6 and related treated with armin and obidoxime, Biochem. 8) Natoff, I. L. and Reiff, B.: Quantitative studies of Spontaneous reactivation and aging of dimethylphospholylated acetylcholinesterase and cholinesterase, Biochemica et Biophysica. Acta, 315, (1973). 5) Jong, L. P. A. and Wolrng, G. Z.: Reactivation of acetylcholinesterase inhibited by 1, 2, 2'-Trimethylpropyl methylphosphonofluoridate (Soman) oximes, Biochem. Pharmacol., 29, (1980). 6) Erdmann, W. D.: Antidotbehandlung bei Alkylphosphatvergflungen, Arch. Toxicol., 24, (1968). 7) Vasic, B. V., Milosevic, M. P. and Terzic, M. R.: Acethylcholine content and cholinesterase activity in the ponto-medullary Pharmacol., 26, (1977). the effect of antagonists region of brain in rats on the acute toxicity of organophosphates in rats, Br. J. Pharmacol., 40, (1970). 9) Hobbiger, F. and Vojvodic: The reactivating and antidotal actions of N, N'-Trimethylenebis (pyridinum-4-aldoxime) (TMB-4) and N, N' - Oxydimethylenebis (pyridinum-4-aldoxime) (Toxogonin), with particular reference to their effect on phosphorylated acetylcholinesterase in the brain, Biochem. Pharmacol., 15, (1966). 10) Mayer, O. and Michalek, H.: Effects of DFP and Obidoxime on brain acetylcholine levels and on brain and peripheral cholinesterase, Biochem. Pharmacol., 20, (1971). 11) Neef, J. H. and Porsius, A. J.: The influence of Obidoxime, Diacetylmonoxime, Pralidoxime and two less hydrophilic derivatives of Pralidoximes upon the cholinesterase inhibition and the pressor effect by paraoxon in the rat, Toxicol. Appl. Pharmacol., 66, (1982). 12) Vasic, B. V., Milosevic, M. P. and Terzic, M. R.: Acetylcholine and cholinesterase in submandibullar glands of rats given armin and obidoxime, J. Dent. Res., 57, (1978).
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